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Tumor flare reaction (TFR) is characterized by an increase in lesion size during immune-based therapy, often resembling disease progression. It signifies inflammation at the tumor site and is frequently seen in immunotherapy, where it is termed "tumor pseudoprogression." The exact mechanisms behind TFR remain unclear. We report the case of a 62-year-old Japanese man with relapsed and refractory diffuse large B cell lymphoma treated with epcoritamab. On day 10 of the first epcoritamab cycle, after two subcutaneous injections of epcoritamab, the cutaneous lymphoma lesions became swollen. This was identified as TFR, and was managed with a three-day course of intravenous dexamethasone at 12 mg/day. The third injection, scheduled for day 15, was delayed by 1 week. Four doses of epcoritamab were completed over the initial 35-day period. A skin biopsy was performed on day 30. Histopathological examination showed CD20+ large atypical lymphocytes forming residual nodules, encircled by CD4+ and CD8+ lymphocytes, with a predominance of CD8+ T cells over CD4+ T cells. Although infrequent, TFR may be a significant indicator of tumor response to epcoritamab therapy. The diagnosis of TFR could be underestimated, and proper identification and understanding of its clinicopathological features are crucial for its effective management.
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ABSTRACT: Ovarian hyperstimulation syndrome (OHSS) is characterized by cystic enlargement of the ovaries and a fluid retention. This syndrome is sometimes caused after in vitro fertilization. We treated a 37-year-old woman with OHSS after in vitro fertilization, coincidentally complicated with acute lymphoblastic leukemia. Her clinical course of acute lymphoblastic leukemia was aggressive with the manifestation of OHSS, such as massive pleural effusion and massive ascites. The leukemic cells broadly infiltrated to the peritoneum, ovary, central spine fluid, and pleura. We speculated that this hyperpermeability of leukemic cells could be associated with the cytokine milieu caused by OHSS.
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Síndrome de Hiperestimulação Ovariana , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Feminino , Adulto , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico por imagem , Gravidez , Síndrome de Hiperestimulação Ovariana/diagnóstico por imagem , Síndrome de Hiperestimulação Ovariana/complicações , Complicações Neoplásicas na Gravidez/diagnóstico por imagemRESUMO
An elevated serum ß2-microglobulin (ß2M) level is indicative of impaired glomerular filtration and prerenal diseases, such as malignant tumors, autoimmune disorders, and liver diseases. An elevated serum ß2M level has been shown to promote metastasis via the induction of epithelial-mesenchymal transition (EMT) in cancer cells. However, the therapeutic potential of targeting ß2M remains unclear. Here, we aimed to investigate the efficacy of Filtor, a small polymethyl methacrylate fiber-based ß2M removal column, in reducing the ß2M level and suppressing cancer cell-induced EMT and metastasis. We assessed the effects of Filtor on the changes in metastasis based on the number of circulating tumor cells (CTCs), which reflects the post-EMT cancer cell population. We performed therapeutic apheresis using Filtor on a male patient with sinonasal neuroendocrine carcinoma, a female patient with a history of colorectal cancer, and another female patient with a history of pancreatic ductal adenocarcinoma. Significantly low serum ß2M levels and CTC counts were observed immediately and 4 weeks after treatment compared with those in the pretreatment phase. Moreover, the CTC count immediately after therapeutic intervention was markedly reduced, likely because Filtor had trapped CTCs directly. These findings suggest that therapeutic apheresis with Filtor can prevent cancer metastasis and recurrence by directly removing CTCs.
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Tixagevimab and cilgavimab (EVA, Evusheld®), monoclonal antibody combination treatments, consisted of two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). EVA showed prophylactic and therapeutic effects against coronavirus disease 2019. The Japanese Society of Hematology recommended EVA for such patients with active treatment, but each institution decided on comprehensive administration. We develop a systematic procedure for comprehensive EVA injection prophylactically in patients with hematological malignancies without any over/under-indication. We listed all patients with the required indications from November 2022 to March 2023. We included 178 cases, 84 females and 94 males, with a median age of 70 (range: 19-90) years. Underlying diseases are myeloid neoplasms in 36 (20%), lymphoid neoplasms in 75 (73%), and others. Indications were intensively hematological malignancy treatment, rituximab treatment within 12 months, burton kinase inhibitor treatment, after chimeric antigen receptor T cell immunotherapy, and after stem cell transplantation in 74 (41%), 73 (41%), 3 (2%), 5 (3%), and 23 (13%) cases, respectively. Of the 178 cases, 22 (12.4%) refused EVA injection. Further, 42 and 136 cases were administered outpatient and inpatient, respectively. Over 95% of the listed cases received EVA injection within 3 months. No severe toxicities were observed among them (N = 156), and 8 (5.2%) cases had breakthrough SARS-CoV-2 infection, which was significantly lower (P = 0.02) than those without EVA (4 [18.2%] of 22 cases). Both groups showed no moderate or severe infection cases. This single-center experience showed that comprehensive EVA injection management effectively generated safer completion with preferable clinical impact.
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COVID-19 , SARS-CoV-2 , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Adulto , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Adulto Jovem , Neoplasias Hematológicas/terapia , Tratamento Farmacológico da COVID-19 , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/uso terapêutico , Doenças Hematológicas/terapia , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
A literature review does not provide information about the safety of autologous hematopoietic stem cell transplantation (HSCT) in a recipient who has previously received allogeneic HSCT. We treated a 69-year-old woman with diffuse large B cell lymphoma. The patient received autologous stem cell transplantation (ASCT) in the second complete remission of malignant lymphoma. The patient had undergone allogeneic hematopoietic SCT (allo-HSCT) for chronic myeloid leukemia 20 years ago. Chronic myeloid leukemia had been in complete remission for the previous 20 years. Thus, the patient received autologous and allogenic HSCT 20 years apart. ASCT involves the patient receiving "self" hematopoietic cells from an allogeneic donor. In other words, this is immunologically the second allo-HSCT. The allo-HSCT 20 years ago was undergone by a related healthy brother, a human leukocyte antigen (HLA) 8/8 full matched donor. The conditioning regimen was reduced-intensity consisting of fludarabine and busulfan. The patient did not experience acute or chronic graft-versus-host disease (GVHD) after allo-HSCT. The second transplantation, ASCT was performed to the MEAM conditioning regimen. Engraftment was uneventful, and complete donor chimerism had been achieved even after ASCT. She suffered from an acute gastric mucosal lesion 52 days after ASCT. Pathological finding of gastric mucosa was nonspecific acute gastritis with significant neutrophil infiltration. Sex chromosome analysis of gastric mucosa demonstrated that mucosal cells had XX signals, whereas infiltrating neutrophils had XY signals. We speculated the patient onset of an acute gastric GVHD in this recipient after the second transplantation. This case remarked infiltration of neutrophils triggered GVHD reaction by resetting allogeneic immune reaction after the second transplantation. We describe a rare occurrence of GVHD reaction in a recipient of ASCT following allo-HSCT.
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Japanese rice cake, mochi, is made from glutinous rice, a very sticky food. Mochi is a popular preserved food during the New Year holiday celebration. However, mochi can be hazardous because of lethal choking or ileus.
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We treated a 78-year-old Japanese man with gastric diffuse large B cell lymphoma. The patient received three courses of chemotherapy and involved-field local radiation therapy to the stomach. Three years after chemotherapy, the patient become sick with anorexia and pancytopenia. He was cachexic, however, levels of vitamin B12, folate, zinc, and copper were normal. His bone marrow revealed focal eosinophilic deposit characterized by mixture of vivid atrophic fatty cells, which was pathologically diagnosed as gelatinous bone marrow. The patient's gelatinous marrow was characterized by CD68-stained vivid atrophic fatty tissue. We found that this finding is a possible alternative marker for gelatinous marrow.
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Japanese noodle 'udon' is an original Asian noodle popular in Japan. Udon is one of the most elastic noodle, and which is required to take more than several hours to digest in a certain case. We encountered a case of enteropathy caused by consumption of udon. A fifteen-year-old girl visited the outpatient clinic with a symptom of epigastralgia persistent from the previous night. She had eaten noodles for dinner the night before. Clinical images showed patient's stomach filled with udon. Noodle-associated enteropathy is not rare in our community, however, there had not been reported in other Asian countries.
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BACKGROUND AIMS: Tacrolimus (TAC) plus short-term methotrexate (stMTX) is used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). TAC blood concentrations are frequently adjusted to enhance the graft-versus-leukemia/lymphoma effect or attenuate severe GVHD. Limited information is available on the clinical impact of these adjustments and the optimal time to perform them in order to achieve good clinical outcomes. METHODS: We retrospectively analyzed 211 patients who underwent allo-HSCT at our institutes. RESULTS: Higher TAC concentrations in week 3 correlated with a significantly higher cumulative incidence of relapse (CIR) (P = 0.03) and lower nonrelapse mortality (P = 0.04). The clinical impact of high TAC concentrations in week 3 on CIR was detected in the refined disease risk index: low/intermediate (P = 0.04) and high (P < 0.01), and conditioning regimens other than cyclophosphamide/total body irradiation and busulfan/cyclophosphamide (P = 0.07). Higher TAC concentrations in week 1 correlated with a lower grade 2-4 acute GVHD rate (P = 0.01). Higher TAC concentrations in weeks 2 and 3 correlated with slightly lower (P = 0.05) and significantly lower (P = 0.02) grade 3-4 acute GVHD rates, respectively. Higher TAC concentrations in weeks 1 and 3 were beneficial for severe acute GVHD in patients with a human leukocyte antigen-matched donor (P = 0.03 and P < 0.01, respectively), not treated with anti-thymocyte globulin (P = 0.02 and P = 0.02, respectively), and receiving three stMTX doses (P = 0.03 and P = 0.02, respectively). CONCLUSIONS: The clinical impact of TAC concentrations varied according to patient characteristics, including disease malignancy, conditioning regimens, donor sources, and GVHD prophylaxis. These results suggest that TAC management needs to be based on patient profiles.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Imunossupressores , Tacrolimo , Condicionamento Pré-Transplante , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Tacrolimo/uso terapêutico , Tacrolimo/sangue , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/tratamento farmacológico , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Imunossupressores/uso terapêutico , Imunossupressores/sangue , Transplante Homólogo/métodos , Adolescente , Condicionamento Pré-Transplante/métodos , Idoso , Metotrexato/uso terapêutico , Adulto JovemRESUMO
Introduction: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare subtype of T-cell leukemia that phenotypically expresses mature T-cell markers and immature myeloid markers such as CD33. Gemtuzumab ozogamicin (GO) is a novel agent for the CD33 molecular targeting antibody conjugated to the cytotoxic agent calicheamicin. GO is anticipated to be effective against ETP-ALL. In vivo studies promise antileukemic effects in cell lines; however, clinical reports to support this research are lacking. We treated a patient who suffered from CD33-positive ETP-ALL using GO. Case Presentation: We treated an 81-year-old man who suffered from ETP-ALL. The patient's leukemia expressed T cell and myeloid markers including cyCD3, CD5, CD7, CD33, and HLA-DR. Initially, the patient was treated using a standard chemotherapy regimen for acute lymphoblastic leukemia comprising cyclophosphamide, daunorubicin, vincristine, l-asparaginase, and prednisolone. The induction chemotherapy produced the expected complete hematological response; however, bone marrow blasts remained. Following consolidation chemotherapy, the patient maintained a full hematological response. Thereafter, we changed the consolidation regimen to nelarabine, which did not reduce bone marrow blasts effectively. After two courses of nelarabine therapy, we finally used GO at an 8 mg/m2 weekly dose after confirming that CD33 expression was still positive in the patient's residual leukemic cells. GO was ineffective in treating the patient's leukemia, and peripheral blasts increased 30 days following treatment. The patient died 81 days after initiating GO therapy. Conclusion: This is the first clinical case of GO having a negative impact on ETP-ALL. Because the GO resistance mechanism for ETP-ALL has not been fully elucidated, treatment modification should be considered to achieve optimal clinical efficacy.
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The typical pleuroparenchymal fibroelastosis (PPFE) after hematopoietic stem cell transplantation (HSCT) is characterized by late-onset progressive pulmonary complication within 5 years. PPFE shows a poor prognosis without definitive standard care other than lung transplantation. Our case indicated an over 20 years late-onset and aggressively exacerbating PPFE.
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Ascites is sometimes detected after allogeneic hematopoietic stem cell transplantation (allo-HSCT); however, since limited information is currently available, its clinical meaning remains unclear. Therefore, we herein examined potential factors for and the impact of ascites on the prognosis of patients after allo-HSCT at our institutes. Fifty-eight patients developed ascites within 90 days of allo-HSCT (small in 34 (16%), moderate-large in 24 (11%)). A multivariate analysis identified veno-occlusive disease/sinusoidal obstruction syndrome (p = 0.01) and myeloablative conditioning (p = 0.01) as significant potential factors for the development of small ascites. Thrombotic microangiopathy (TMA) (p < 0.01) was a significant potential factor for moderate-large ascites. The incidence of both small and moderate-large ascites correlated with lower overall survival (p = 0.03 for small ascites and p < 0.01 for moderate-large ascites) and higher non-relapse mortality rates (p = 0.03 for small ascites and p < 0.01 for moderate-large ascites). Lower OS and higher NRM rates correlated with the incidence of both small and moderate-large ascites. Further investigation is warranted to establish whether the clinical sign of ascites improves the diagnostic quality of TMA in a large-scale study.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Humanos , Prognóstico , Ascite/complicações , Fatores de Risco , Doença Enxerto-Hospedeiro/diagnóstico , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/etiologia , Condicionamento Pré-Transplante/efeitos adversosRESUMO
BACKGROUND: Acute myeloid leukemia (AML) is a progressive hematological malignancy that can be fatal when left untreated. However, spontaneous remission is rarely observed in the presence of infectious diseases. CASE PRESENTATION: We treated an 80-year-old woman with AML who spontaneously underwent remission after infections. Spontaneous remission was observed after each of three independent clinical infections caused by different pathogens-nontuberculous Mycobacterium infection, pulmonary aspergillosis, and Escherichia coli bacteremia. All infections were treated promptly with antimicrobials. Mycobacterium avium infection was treated with azithromycin, rifampin, and ethambutol. Pulmonary aspergillosis was treated with itraconazole followed by voriconazole. E. coli infection was treated with meropenem. During each infectious episode, leukemic cells disappeared from the patient's peripheral blood and pancytopenia improved without routine blood transfusion. These clinical effects lasted for several months. The patient has survived for > 2 years beyond the median survival time of end-stage AML. Thus, this case represents an immunological antileukemic effect of systemic infections. CONCLUSIONS: We have discussed a common mechanism of spontaneous remission of AML without chemotherapy, clinically exhibited by infection immunology. We believe that infections exert a limited immunological effect against AML, which may prolong survival among elderly individuals with AML.